We have approved your request to supplement your biologics license application for Human Immunodeficiency Virus Type 1 and/or Hepatitis C Virus and/or Hepatitis B Virus (HIV-1 and HCV and HBV/Nucleic Acid Pooled Testing/Synthetic) to include the Procleix Ultrio Plus Assay, a qualitative in vitro nucleic acid amplification test for use on the PROCLEIX TIGRIS System, to screen for Human Immunodeficiency Virus Type 1 (HIV-1) RNA, Hepatitis C Virus (HCV) RNA, and Hepatitis B Virus (HBV) DNA in plasma and serum specimens from individual human donors, including donors of whole blood, blood components, and source plasma, and from other living donors. It is also intended for use in testing plasma and serum specimens to screen organ donors when specimens are obtained while the donor's heart is still beating, and in testing blood specimens from cadaveric (non-heart-beating) donors.

The assay is intended for use in testing individual samples from living donors of whole blood, blood components, and source plasma, other living donors and heart-beating organ donors, and for testing individual blood specimens from cadaveric (non-heart-beating) donors. It is also intended for use in testing pools of human plasma comprised of equal aliquots of not more than 16 individual donations from donors of whole blood, blood components, and source plasma. It is also intended for use in testing pools of human plasma comprised of equal aliquots of not more than 16 individual specimens from donors of hematopoietic stem/ progenitor cells (HPCs) sourced from bone marrow, peripheral blood or cord blood, and from donors of donor lymphocytes for infusion (DLI). This assay is intended to be used in conjunction with licensed tests for detecting antibodies to HIV-1, HCV, and hepatitis B core antigen (anti-HBc), and with licensed tests for hepatitis B surface antigen (HBsAg).

The assay is not intended for use on cord blood specimens. This assay is not intended for use as an aid in diagnosis of infection with HIV-1, HCV or HBV.

The PROCLEIX ULTRIO PLUS Assay can be considered a supplemental test that confirms HIV-1 infection for specimens that are repeatedly reactive on a licensed donor screening test for antibodies to HIV-1, and reactive on both the PROCLEIX ULTRIO PLUS Assay and on the PROCLEIX ULTRIO PLUS HIV-1 Discriminatory Assay.

The PROCLEIX ULTRIO PLUS Assay can be considered a supplemental test that confirms HCV infection for specimens that are repeatedly reactive on a licensed donor screening test for antibodies to HCV, and reactive on both the PROCLEIX ULTRIO PLUS Assay and on the PROCLEIX ULTRIO PLUS HCV Discriminatory Assay.

The PROCLEIX ULTRIO PLUS Assay can be considered a supplemental test that confirms HBV infection for specimens that are repeatedly reactive on a licensed donor screening test for HBsAg, and reactive on both the PROCLEIX ULTRIO PLUS Assay and on the PROCLEIX ULTRIO PLUS HBV Discriminatory Assay.

You are approved to manufacture Human Immunodeficiency Virus Type 1 and/or Hepatitis C Virus and/or Hepatitis B Virus (HIV-1 and HCV and HBV/Nucleic Acid Pooled Testing/Synthetic) at the following facilities: -----b(4)---------------------------------------------------------------------------------- Genetic Center Drive Facility, 10210 Genetic Center Drive, San Diego, CA 92121. You may label your product with the proprietary name PROCLEIX ULTRIO PLUS Assay that we have approved and market it as approved in your license application.

The dating period for the PROCLEIX ULTRIO PLUS Assay shall be 24 months from the date of manufacture when stored at 2-8 °C. The date of manufacture shall be defined in accordance with 21 CFR 610.50. The expiration date for the packaged product, PROCLEIX ULTRIO PLUS Assay, shall be dependent on the shortest expiration date of any component.

Please submit final container samples of the product in final containers together with protocols showing results of all applicable tests. You may not distribute any lots of product until you receive a notification of release from the Director, Center for Biologics Evaluation and Research (CBER).

You must submit information to your biologics license application for our review and written approval under 21 CFR 601.12 for any changes in, including but not limited to, the manufacturing, testing, packaging or labeling of Human Immunodeficiency Virus Type 1 and/or Hepatitis C Virus and/or Hepatitis B Virus (HIV-1 and HCV and HBV/Nucleic Acid Pooled Testing/Synthetic) or in the manufacturing facilities.

You must submit reports of biological product deviations under 21 CFR 600.14. You promptly should identify and investigate all manufacturing deviations, including those associated with processing, testing, packing, labeling, storage, holding and distribution. If the deviation involves a distributed product, may affect the safety, purity, or potency of the product, and meets the other criteria in the regulation, you must submit a report on Form FDA 3486 to the Director, Office of Compliance and Biologics Quality, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Rockville, MD 20852-1448.

Please submit all final printed labeling at the time of use and include implementation information on Form FDA 356h. Please provide a PDF electronic copy as well as three original paper copies for circulars and other labels.

Two draft copies of the proposed introductory promotional labeling may be voluntarily submitted for advisory comment with a Form FDA 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448.

ADVERSE EVENT REPORTING

You must submit adverse experience reports in accordance with the Medical Device Reporting requirements for medical devices (21 CFR 803) as required by 21 CFR 600.80(k)(2). Since your product is characterized as a device as well as a biological, submit these reports to the MedWatch System using MedWatch Reporting Form 3500A. Required reports should be submitted to the Food and Drug Administration, Center for Devices and Radiological Health, Medical Device Reporting, P.O. Box 3002, Rockville, MD 20847-3002.

Gen-Probe will submit the results from this testing to FDA within six months of approval of this efficacy supplement. Please label the submission with the following designator: Postmarketing Study Commitment – Final Study Report

We request that you submit information concerning nonclinical and chemistry, manufacturing, and controls postmarketing commitments and final reports to your BLA, STN BL 125113.